Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.
AffiliationDepartment of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland.
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CitationEstrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon. 2011:notSteroids
AbstractExcessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17β-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17β-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17β-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCδ activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17β-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17β-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCδ-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17β-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.
- Female gender-specific inhibition of KCNQ1 channels and chloride secretion by 17beta-estradiol in rat distal colonic crypts.
- Authors: O'Mahony F, Alzamora R, Betts V, LaPaix F, Carter D, Irnaten M, Harvey BJ
- Issue date: 2007 Aug 24
- Guanosine 3',5'-cyclic monophosphate-dependent protein kinase II mediates heat-stable enterotoxin-provoked chloride secretion in rat intestine.
- Authors: Vaandrager AB, Bot AG, De Jonge HR
- Issue date: 1997 Feb
- K+ channel KVLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl- secretion.
- Authors: Liao T, Wang L, Halm ST, Lu L, Fyffe RE, Halm DR
- Issue date: 2005 Sep
- Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent CI(−) secretion across rat distal colonic mucosa.
- Authors: Wu D, Zhou J, Wang X, Cui B, An R, Shi H, Yuan J, Hu Z
- Issue date: 2011 Mar 24
- Levamisole inhibits intestinal Cl- secretion via basolateral K+ channel blockade.
- Authors: Mun EC, Mayol JM, Riegler M, O'Brien TC, Farokhzad OC, Song JC, Pothoulakis C, Hrnjez BJ, Matthews JB
- Issue date: 1998 Jun